IV.A. Actions of GI hormones on gastric chief cells. IV.A.1. Action of bombesin on gastric chief cells. Bombesin-related peptides in vivo stimulate pepsinogen release however it is unclear whether it is due to a direct action on chief cells or an indirect action. To attempt to address this question, we studied the action of bombesin-related peptides on isolated guinea pig chief cells. Bombesin- related peptides (Bn, GRP, NMB) did not stimulate pepsinogen release, alter [Ca2+], cAMP or inositol phosphate levels alone or effect stimulation by other agents. Very low levels of binding were seen suggesting binding to contaminating cells. These results demonstrate bombesin related peptides do not alter pepsinogen release by direct interaction with chief cells. IV.B Actions of GI hormones on gastric smooth muscle cells. IV. B.1. Somatostatin (SS) receptor subtypes on gastric smooth muscle cells. Gastric smooth muscle cells are shown to possess high affinity SS receptors. Smooth muscle cells rapidly degraded SS-14, however with appropriate protein inhibitors present and the use of a peptidase resistant ligand the pharmacology and stoichiometry of the SS receptors were explored. The receptor exists in 2 affinity states which are regulated by a G-protein. In collaboration with Dr. D.H. Coy (Tulane University) using SS receptor subtype specific analogues, the action of SS on these cells wa s shown to be mediated by the SSTR-3 subtype. IV.2. Mechanism of galanin-induced relaxation. Recently, GI smooth muscle cell relaxants have been shown in some cases to both activate adenylate cyclase and NO synthetase. In isolated guinea pig gastric smooth muscle cells both VIP and galanin caused equipotent relaxation. Using NO synthetase and PKA inhibitors our results demonstrate galanin's relaxant effect is mediated only by cAMP whereas VIP both activates adenylate cyclase and nitric oxide synthetase.
